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Stent restenosis is an infrequent but poorly understood clinical problem in the drug-eluting stent era. The aim of the study was to evaluate the morphologic characteristics of stent restenosis by optical coherence tomography (OCT). Patients (n = 24, 25 vessels) presenting with angiographically documented stent restenosis were included. Quantitative OCT analysis consisted of lumen and stent area measurement and calculation of restenotic tissue area and burden. Qualitative restenotic tissue analysis included assessment of tissue structure, backscattering and symmetry, visible microvessels, lumen shape, and presence of intraluminal material. By angiography, restenosis was classified as diffuse, focal, and at the margins in 9, 11, and 5 vessels, respectively. By OCT, restenotic tissue structure was layered in 52%, homogeneous in 28%, and heterogeneous in 20%. The predominant backscatter was high in 72%. Microvessels were visible in 12%. Lumen shape was irregular in 28% and there was intraluminal material in 20%. The mean restenotic tissue symmetry ratio was 0.58 ± 0.19. Heterogeneous and low scattering restenotic tissue was more frequent in focal (45.5% and 54.5%, respectively) than in diffuse (0 and 11.1%) and margin restenosis (0 and 0%) ( P = .005 for heterogeneous, P = .03 for low scattering). Restenosis patients with unstable angina symptoms presented more frequently irregular lumen shape (60 vs 6.7%, P = .007). Stents implanted ≤12 months ago had more frequently restenotic tissue with layered appearance (84.6% vs 16.7%, P = .003). We demonstrate the ability of OCT to identify differential patterns of restenotic tissue after stenting. This information could help in understanding the mechanism of stent restenosis.

Drug-eluting metallic coronary stents predispose to late stent thrombosis, prevent late lumen vessel enlargement, hinder surgical revascularisation, and impair imaging with multislice CT. We assessed the safety of the bioabsorbable everolimus-eluting stent (BVS). 30 patients with a single de-novo coronary artery lesion were followed up for 2 years clinically and with multiple imaging methods: multislice CT, angiography, intravascular ultrasound, derived morphology parameters (virtual histology, palpography, and echogenicity), and optical coherence tomography (OCT). Clinical data were obtained from 29 of 30 patients. At 2 years, the device was safe with no cardiac deaths, ischaemia-driven target lesion revascularisations, or stent thromboses recorded, and only one myocardial infarction (non-Q wave). 18-month multislice CT (assessed in 25 patients) showed a mean diameter stenosis of 19% (SD 9). At 2-year angiography, the in-stent late loss of 0·48 mm (SD 0·28) and the diameter stenosis of 27% (11) did not differ from the findings at 6 months. The luminal area enlargement on OCT and intravascular ultrasound between 6 months and 2 years was due to a decrease in plaque size without change in vessel size. At 2 years, 34·5% of strut locations presented no discernible features by OCT, confirming decreases in echogenicity and in radiofrequency backscattering; the remaining apparent struts were fully apposed. Additionally, vasomotion occurred at the stented site and adjacent coronary artery in response to vasoactive agents. At 2 years after implantation the stent was bioabsorbed, had vasomotion restored and restenosis prevented, and was clinically safe, suggesting freedom from late thrombosis. Late luminal enlargement due to plaque reduction without vessel remodelling needs confirmation. Abbott Vascular (USA).

A fully bioabsorbable drug-eluting coronary stent that scaffolds the vessel wall when needed and then disappears once the acute recoil and constrictive remodelling processes have subsided has theoretical advantages. The bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid that provides the support and a coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus. We assessed the feasibility and safety of this BVS stent. In this prospective, open-label study we enrolled 30 patients who had either stable, unstable, or silent ischaemia and a single de-novo lesion that was suitable for treatment with a single 3·0×12 mm or 3·0×18 mm stent. Patients were enrolled from four academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite endpoint was cardiac death, myocardial infarction, and ischaemia-driven target lesion revascularisation. Angiographic endpoints were available for 26 patients and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients, optical coherence tomography was undertaken at baseline and follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00300131. Procedural success was 100% (30/30 patients), and device success 94% (29/31 attempts at implantation of the stent). At 1 year, the rate of major adverse cardiac events was 3·3%, with only one patient having a non-Q wave myocardial infarction and no target lesion revascularisations. No late stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent late loss was 0·44 (0·35) mm and was mainly due to a mild reduction of the stent area (−11·8%) as measured by intravascular ultrasound. The neointimal area was small (0·30 [SD 0·44] mm 2), with a minimal area obstruction of 5·5%. This study shows the feasibility of implantation of the bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss, minimal intrastent neointimal hyperplasia, and a low stent area obstruction. Abbott Vascular.

Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialisation of the stent struts. We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus-eluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.

Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients’ responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES.

The relation between C-reactive protein (CRP) and coronary atherosclerosis is not fully understood. This study aims to investigate the associations among high-sensitivity CRP, coronary plaque burden, and the presence of high-risk coronary lesions as measured by intravascular ultrasound (IVUS) and 1-year cardiovascular outcome. Between 2008 and 2011, grayscale and virtual histology IVUS imaging of a nonculprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris. Primary end point consisted of 1-year major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or unplanned coronary revascularization. After adjustment for established cardiac risk factors, baseline CRP levels were independently associated with higher coronary plaque burden (p = 0.002) and plaque volume (p = 0.002) in the imaged coronary segment. CRP was also independently associated with the presence of large lesions (plaque burden ≥70%; p = 0.030) but not with the presence of stenotic lesions (minimal luminal area ≤4.0 mm2; p = 0.62) or IVUS virtual histology-derived thin-cap fibroatheroma lesions (p = 0.36). Cumulative incidence of 1-year MACE was 9.7%. CRP levels >3 mg/L were independently associated with a higher incidence of MACE (hazard ratio 2.17, 95% confidence interval [CI] 1.01 to 4.67, p = 0.046) and of all-cause mortality and ACS only (hazard ratio 3.58, 95% CI 1.04 to 13.0, p = 0.043), compared with CRP levels <1 mg/L. In conclusion, in patients who underwent coronary angiography, high-sensitivity CRP is a marker of coronary plaque burden but is not related to the presence of virtual histology-derived thin-cap fibroatheroma lesions and stenotic lesions. CRP levels >3 mg/L are predictive for adverse cardiovascular outcome at 1 year.

PurposeQuantitative and automatic analysis of intracoronary optical coherence tomography images is useful and time-saving to assess cardiovascular risk in the clinical arena.MethodsFirst, the interfaces of the intima, media, and adventitia layers are segmented, by means of an original front propagation scheme, running in a 4D multi-parametric space, to simultaneously extract three non-crossing contours in the initial cross-sectional image. Second, information resulting from the tentative contours is exploited by a machine learning approach to identify healthy and diseased regions of the arterial wall. The framework is fully automatic.ResultsThe method was applied to 40 patients from two different medical centers. The framework was trained on 140 images and validated on 260 other images. For the contour segmentation method, the average segmentation errors were 29±46μm for the intima–media interface, 30±50μm for the media–adventitia interface, and 50±64μm for the adventitia–periadventitia interface. The classification method demonstrated a good accuracy, with a median Dice coefficient equal to 0.93 and an interquartile range of (0.78–0.98).ConclusionThe proposed framework demonstrated promising offline performances and could potentially be translated into a reliable tool for various clinical applications, such as quantification of tissue layer thickness and global summarization of healthy regions in entire pullbacks.

Over the last few years, treatment of severe symptomatic aortic stenosis in high-risk patients has drastically changed to adopt a less-invasive approach. Transcatheter aortic valve implantation (TAVI) has been developed as a very reproducible and safe procedure, as shown in many trials. When compared to surgery, TAVI has produced superior, or at least comparable, results, and thus a trend to broaden treatment indications to lower-risk patients has erupted as a natural consequence, even though there is a lack of long-term evidence. In this review, we summarize and underline aspects that still remain unanswered that are compulsory if we want to enhance our understanding of this disease.

Lipid-core atherosclerotic plaques are associated with disease progression, procedural complications, and cardiac events. Coronary plaque lipid can be quantified in optical coherence tomography (OCT) pullbacks by measurement of lipid arcs and lipid lengths; parameters frequently used in clinical research, but labor intensive and subjective to analyse. In this study, we investigated the ability of quantitative attenuation, derived from intravascular OCT, to detect plaque lipid. Lipid cores are associated with a high attenuation coefficient. We compared the index of plaque attenuation (IPA), a local quantitative measure of attenuation, to the manually measured lipid score (arc and length) on OCT images, and to the plaque characterization ex-vivo. We confirmed a correlation between the IPA and lipid scores (r 2  > 0.7). Comparison to histology shows that high attenuation is associated with fibroatheroma, but also with macrophage presence. IPA is a robust, reproducible, and user-independent measure that facilitates quantification of coronary lipid, a potential tool in clinical research and in guiding percutaneous coronary intervention.

This study aimed to evaluate the relationship between cigarette smoking and coronary atherosclerotic burden, volume and composition as determined in-vivo by grayscale and virtual histology (VH) intravascular ultrasound (IVUS). Between 2008 and 2011, (VH-)IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. To account for differences in baseline characteristics, current smokers were matched to never smokers by age, gender and indication for catheterization, resulting in 280 patients available for further analysis. Coronary atherosclerotic plaque volume, burden, composition (fibrous, fibro-fatty, dense calcium and necrotic core) and high-risk lesions (VH-IVUS derived thin-cap fibroatheroma (TCFA), plaque burden ≥70%, minimal luminal area ≤4.0 mm2) were assessed. Cigarette smoking showed a tendency towards higher coronary plaque burden (mean±SD, 38.6±12.5% in current versus 36.4±11.0% in never smokers, p = 0.080; and odds ratio (OR) of current smoking for plaque burden above versus below the median 1.69 (1.04-2.75), p = 0.033). This effect was driven by an association in patients presenting with an acute coronary syndrome (ACS) (current smokers, plaque burden 38.3±12.8% versus never smokers, plaque burden 35.0±11.2%, p = 0.049; OR 1.88 (1.02-3.44), p = 0.042). Fibrous tissue tended to be lower in current smokers (mean±SD, 57.7±10.5% versus 60.4±12.6%, p = 0.050) and fibro-fatty tissue was higher in current smokers (median[IQR], 9.6[6.0-13.7]% versus 8.6[5.8-12.2]%, p = 0.039). However, differences in percentage necrotic core and dense calcium could not be demonstrated. Also, no differences were found with regard to high-risk lesions. An association between smoking and degree of coronary atherosclerosis was present in patients undergoing coronary angiography who presented with ACS. Although smoking was associated with higher fibro-fatty percentage, no associations could be demonstrated with percentage necrotic core, nor with VH-IVUS derived TCFA lesions. Since the magnitude of the differences in both degree and composition of atherosclerosis was modest, clinical relevance of the findings may be questioned.